Substance P protects spiral ganglion neurons from apoptosis via PKC-Ca2+-MAPK/ERK pathways

[en] In the current study, we have investigated the ability of substance P (SP) to protect 3-day-old (P3) rat spiral ganglion neurons (SGNs) from trophic factor deprivation (TFD)-induced cell death. The presence of SP high affinity neurokinin-1 receptor (NK1) transcripts was detected in the spiral ganglion and the NK1 protein localized to SGNs both ex vivo and in vitro. Treatment with SP increased cytoplasmic Ca2+ in SGNs, further arguing for the presence of functional NK1 on these neurons. Both SP and the agonist [Sar(9), Met(O-2)(11)]-SP significantly decreased SGN cell death induced by TFD, with no effect on neurite outgrowth. The survival promoting effect of SP was blocked by the NK1 antagonist, WIN51708. Both pan-caspase inhibitor BOC-D-FMK and SP treatments markedly reduced activation of caspases and DNA fragmentation in trophic factor deprived-neurons. The neuroprotective action of SP was antagonised by specific inhibitors of second messengers, including 1.2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, the protein kinase C (PKC) inhibitors bisindolylmaleimide I, Go6976 and LY333531 and the MAPK/ERK inhibitor U0126. In contrast, nifedipine, a specific inhibitor of L-type Ca2+ channel, and LY294002, a phosphatidylinositol-3-OH kinase (PI3K) inhibitor, had no effect on SP trophic support of SGNs. Moreover, activation of endogenous PKC by 4beta-phorbol 12-myristate 13-acetate (PMA) also reduced the loss of trophic factor-deprived SGNs. Thus, NK1 expressed by SGNs transmit a survival-promoting regulatory signal during TFD-induced SGN cell death via pathways involving PKC activation, Ca2+ signalling and MAPK/ERK activation, which can be accounted for by an inhibition of caspase activation.

Research Center/Unit :

Giga-Neurosciences - ULiège

Disciplines :

Neurosciences & behavior
Biochemistry, biophysics & molecular biology

Author, co-author :

Lallemend, François

Lefèbvre, Philippe ; Université de Liège - ULiège > Département des sciences cliniques > Oto-rhino-laryngologie et audiophonologie

Hans, Grégory ; Université de Liège - ULiège > Anesthésie et réanimation

Rigo, Jean-michel

Van De Water, T. R.

Moonen, Gustave ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie - Doyen de la Faculté de Médecine

Malgrange, Brigitte ; Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc.

Language :

English

Title :

Substance P protects spiral ganglion neurons from apoptosis via PKC-Ca2+-MAPK/ERK pathways

Publication date :

October 2003

Journal title :

Journal of Neurochemistry

ISSN :

0022-3042

eISSN :

1471-4159

Publisher :

Blackwell Publishing Ltd, Oxford, United Kingdom

Volume :

Issue :

Pages :

508-521

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique

Available on ORBi :

since 25 November 2009

Statistics

Number of views

103 (2 by ULiège)

Number of downloads

3 (3 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

d'Aldin C., Puel J. L., Leducq R., Crambes O., Eybalin M. and Pujol R. (1995) Effects of a dopaminergic agonist in the guinea pig cochlea. Hear Res. 90, 202-211.
Appell K. C., Fragale B. J., Loscig J., Singh S. and Tomczuk B. E. (1992) Antagonists that demonstrate species differences in neurokinin-1 receptors. Mol. Pharmacol. 41, 772-778.
Ballif B. A. and Blenis J. (2001) Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK cell survival signals. Cell Growth Diff. 12, 397-408.
Baranauskas G. and Nistri A. (1998) Sensitization of pain pathways in the spinal cord: cellular mechanisms. Prog. Neurobiol. 54, 349-365.
Barker R. (1991) Substance-P and neurodegenerative disorders - a speculative review. Neuropeptides 20, 73-78.
Bedner E., Smolewski P., Amstad P. and Darzynkiewiez Z. (2000) Activation of caspases measured in situ by binding of fluorochrome-labeled inhibitors of caspases (FLICA): correlation with DNA fragmentation. Exp. Cell Res. 259, 308-313.
Belcheva M. M., Gucker S., Chuang D. M., Clark W. G., Jefcoat L. B., Mchale R. J., Toth G., Borsodi A. and Coscia C. J. (1995) Modulation of opioid binding associated with nuclear matrix and nuclear-membranes of Ng108-15 cells. J. Pharmacol. Exp. Ther. 274, 1513-1523.
Berridge M. J. (1993) Inositol trisphosphate and calcium signalling. Nature 361, 315-325.
Berts A., Zhong H. and Minneman K. P. (1999) No role for Ca++ or protein kinase C in alpha-1A adrenergic receptor activation of mitogen-activated protein kinase pathways in transfected PC12 cells. Mol. Pharmacol. 55, 296-303.
Bockmann S., Seep J. and Jonas L. (2001) Delay of neutrophil apoptosis by the neuropeptide substance P: involvement of caspase cascade. Peptides 22, 661-670.
Bottenstein J. E. and Sato G. H. (1979) Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc. Natl. Acad. Sci. USA 76, 514-517.
Calvo N., Reiriz J., Perez-Navarro E. and Alberch J. (1996) Tachykinins protect cholinergic neurons from quinolinic acid excitotoxicity in striatal cultures. Brain Res. 740, 323-328.
Choe Y., Lee B. J. and Kim K. (2002) Participation of protein kinase C alpha isoform and extracellular signal-regulated kinase in neurite outgrowth of GT1 hypothalamic neurons. J. Neurochem. 83, 1412-1422.
Collins F., Schmidt M. F., Guthrie P. B. and Kater S. B. (1991) Sustained increase in intracellular calcium promotes neuronal survival. J. Neurosci. 11, 2582-2587.
Crespo P., Xu N., Daniotti J. L., Troppmair J., Rapp U. R. and Gutkind J. S. (1994) Signaling through transforming G protein-coupled receptors in NIH 3T3 cells involves c-Raf activation. Evidence for a protein kinase C-independent pathway. J. Biol. Chem. 269, 21103-21109.
De Felipe C., Pinnock R. D. and Hunt S. P. (1995) Modulation of chemotropism in the developing spinal cord by substance P. Science 267, 899-902.
Dhanasekaran N., Tsim S. T., Dermott J. M. and Onesime D. (1998) Regulation of cell proliferation by G proteins. Oncogene 17, 1383-1394.
Dimri R., Sharabi Y. and Shoham J. (2000) Specific inhibition of glucocorticoid-induced thymocyte apoptosis by substance P. J. Immunol. 164, 2479-2486.
Dudek H., Datta S. R., Franke T. F., Birnbaum M. J., Yao R. J., Cooper G. M., Segal R. A., Kaplan D. R. and Greenberg M. E. (1997) Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 275, 661-665.
Egea J., Espinet C., Soler R. M., Dolcet X., Yuste V. J., Encinas M., Iglesias M., Rocamora N. and Comella J. X. (2001) Neuronal survival induced by neurotrophins requires calmodulin. J. Cell Biol. 154, 585-597.
Elliott-Hunt C. R., Kazlauskaite J., Wilde G. J. C., Grammatopoulos D. K. and Hillhouse E. W. (2002) Potential signalling pathways underlying corticotrophin-releasing hormone-mediated neuroprotection from excitotoxicity in rat hippocampus. J. Neurochem. 80, 416-425.
Ernfors P., Van De W. T. Loring J. and Jaenisch R. (1995) Complementary roles of BDNF and NT-3 in vestibular and auditory development. Neuron 14, 1153-1164.
Eybalin M. (1993) Neurotransmitters and neuromodulators of the mammalian cochlea. Physiol. Rev. 73, 309-373.
Fanarraga M. L., Avila J. and Zabala J. C. (1999) Expression of unphosphorylated class III beta-tubulin isotype in neuroepithelial cells demonstrates neuroblast commitment and differentiation. Eur. J. Neurosci. 11, 517-527.
Gaborjan A., Lendvai B. and Vizi E. S. (1999) Neurochemical evidence of dopamine release by lateral olivocochlear efferents and its presynaptic modulation in guinea-pig cochlea. Neuroscience 90, 131-138.
Gomez T. M., Robles E., Poo M. and Spitzer N. C. (2001) Filopodial calcium transients promote substrate-dependent growth cone turning. Science 291, 1983-1987.
Grafe M. R., Forno L. S. and Leng L. F. (1985) Immunocytochemical studies of substance P and Met-enkephalin in the basal ganglia and substantia nigra in Huntington's, Parkinson's and Alzheimer's diseases. J. Neuropathol. Exp. Neurol. 44, 47-59.
Gubina E., Rinaudo M. S., Szallasi Z., Blumberg P. M. and Mufson R. A. (1998) Overexpression of protein kinase C isoform epsilon but not delta in human interleukin-3-dependent cells suppresses apoptosis and induces bcl-2 expression. Blood 91, 823-829.
Hawes B. E., Vanbiesen T., Koch W. J., Luttrell L. M. and Lefkowitz R. J. (1995) Distinct pathways of G(I)-mediated and G(Q)-mediated mitogen-activated protein-kinase activation. J. Biol. Chem. 270, 17148-17153.
Hetman M., Kanning K., Cavanaugh J. E. and Xia Z. (1999) Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. J. Biol. Chem. 274, 22569-22580.
Hisashi K., Nakagawa T., Yasuda T., Kimitsuki T., Komune S. and Komiyama S. (1995) Voltage-dependent Ca2+ channels in the spiral ganglion cells of guinea pig cochlea. Hear Res. 91, 196-201.
Hokfelt T., Kellerth J. O., Nilsson G. and Pernow B. (1975) Substance P: localization in the central nervous system and in some primary sensory neurons. Science 190, 889-890.
Hokfelt T., Vincent S., Hellsten L., Rosell S., Folkers K., Markey K., Goldstein M. and Cuello C. (1981) Immunohistochemical evidence for a 'neurotoxic' action of (D-Pro2, D-Trp7,9)-substance P, an analogue with substance P antagonistic activity. Acta Physiol. Scand. 113, 571-573.
Hokfelt T., Broberger C., Xu Z. Q., Sergeyev V., Ubink R. and Diez M. (2000) Neuropeptides - an overview. Neuropharmacology 39, 1337-1356.
Ito K., Rome C., Bouleau Y. and Dulon D. (2002) Substance P mobilizes intracellular calcium and activates a nonselective cation conductance in rat spiral ganglion neurons. Eur. J. Neurosci. 16, 2095-2102.
Iwasaki Y., Kinoshita M., Ikeda K., Takamiya K. and Shiojima T. (1989) Trophic effect of various neuropeptides on the cultured ventral spinal cord of rat embryo. Neurosci. Lett. 101, 316-320.
Jenkinson K. M., Southwell B. R. and Furness J. B. (1999) Two affinities for a single antagonist at the neuronal NK1 tachykinin receptor: evidence from quantitation of receptor endocytosis. Br. J. Pharmacol. 126, 131-136.
Jirousek M. R., Gillig J. R., Gonzalez C. M. et al. (1996) (S)-13-[(dimethylamino) methyl]-10,11,14,15-tetrahydro-4,9:16,21-dime-theno-1H,13H-dibenzo[e,k] pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-dione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta. J. Med. Chem. 39, 2664-2671.
Johannes F. J., Prestle J., Eis S., Oberhagemann P. and Pfizenmaier K. (1994) Pkcu is a novel, atypical member of the protein-kinase-C family. J. Biol. Chem. 269, 6140-6148.
Kang B. N., Jeong K. S., Park S. J., Kim S. J., Kim T. H., Kim H. J. and Ryu S. Y. (2001) Regulation of apoptosis by somatostatin and substance P in peritoneal macrophages. Regul. Pept. 101, 43-49.
Khawaja A. M. and Rogers D. F. (1996) Tachykinins: receptor to effector. Int. J. Biochemem. Cell Biol. 28, 721-738.
Komuro H. and Rakic P. (1996) Intracellular Ca2+ fluctuations modulate the rate of neuronal migration. Neuron 17, 275-285.
Kopke R., Staecker H., Lefebvre P., Malgrange B., Moonen G., Ruben R. J. and Van de Water T. R. (1996) Effect of neurotrophic factors on the inner ear: clinical implications. Acta Otolaryngol. (Stockh.) 116, 248-252.
Kowall N. W., Beal M. F., Busciglio J., Duffy L. K. and Yankner B. A. (1991) An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P. Proc. Natl. Acad. Sci. USA 88, 7247-7251.
Kozlova M. V. I., I'inskii O. B., Kalenchuk V. U. and Kondrikova E. S. (1986) Activating effect of substance P on nerve tissue in culture. Neirofiziologiia 18, 610-615.
Lai J. P., Zhan G. X., Campbell D. E., Douglas S. D. and Ho W. Z. (2000) Detection of substance P and its receptor in human fetal microglia. Neuroscience 101, 1137-1144.
Lefebvre P. P., Malgrange B., Staecker H., Moghadass M., Van de Water T. R. and Moonen G. (1994) Neurotrophins affect survival and neuritogenesis by adult injured auditory neurons in vitro. Neuroreport 5, 865-868.
Lefebvre P. P., Weber T., Rigo J. M., Staecker H., Moonen G. and Van de Water T. R. (1992) Peripheral and central target-derived trophic factor(s) effects on auditory neurons. Hear Res. 58, 185-192.
Lev S., Moreno H., Martinez R., Canoll P., Peles E., Musacchio J. M., Plowman G. D., Rudy B. and Schlessinger J. (1995) Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature 376, 737-745.
LopezIlasaca M., Crespo P., Pellici P. G., Gutkind J. S. and Wetzker R. (1997) Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma. Science 275, 394-397.
Luo W., Sharif T. and Sharif M. (1996) Substance P-induced mitogenesis in human astrocytoma cells correlates with activation of the mitogen-activated protein kinase signaling pathway. Cancer Res. 56, 4983-4991.
Macdonald S. G., Dumas J. J. and Boyd N. D. (1996) Chemical cross-linking of the substance P (NK-1) receptor to the alpha subunits of the G proteins Gq and G11. Biochemistry 35, 2909-2916.
Malgrange B., Lefebvre P., Van de Water T. R., Staecker H. and Moonen G. (1996) Effects of neurotrophins on early auditory neurones in cell culture. Neuroreport 7, 913-917.
Marinissen M. J. and Gutkind J. S. (2001) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol. Sci. 22, 368-376.
Marquardt B., Frith D. and Stabel S. (1994) Signaling from Tpa to map kinase requires protein-kinase-C, Raf and Mek - reconstitution of the signaling pathway in-vitro. Oncogene 9, 3213-3218.
Martiny-Baron G., Kazanietz M. G., Mischak H., Blumberg P. M., Kochs G., Hug H., Marme D. and Schachtele C. (1993) Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976. J. Biol. Chem. 268, 9194-9197.
Mcconkey D. J., Hartzell P., Jondal M. and Orrenius S. (1989) Inhibition of DNA fragmentation in thymocytes and isolated thymocyte nuclei by agents that stimulate protein kinase-C. J. Biol. Chem. 264, 13399-13402.
Mellor H. and Parker P. J. (1998) The extended protein kinase C superfamily. Biochem. J. 332, 281-292.
Mochizuki-Oda N., Nakajima Y., Nakanishi S. and Ito S. (1994) Characterization of the substance P receptor-mediated calcium influx in cDNA transfected Chinese hamster ovary cells. A possible role of inositol 1,4,5-trisphosphate in calcium influx. J. Biol. Chem 269, 9651-9658.
Narumi S. and Maki Y. (1978) Stimulatory effects of substance P on neurite extension and cyclic AMP levels in cultured neuroblastoma cells. J. Neurochem. 30, 1321-1326.
Newton A. C. (1997) Regulation of protein kinase C. Curr. Opin. Cell Biol. 9, 161-167.
Nishizuka Y. (1995) Protein kinases 5. Protein-kinase-C and lipid signaling for sustained cellular-responses. FASEB J. 9, 484-496.
Noveral J. P. and Grunstein M. M. (1995) Tachykinin regulation of airway smooth-muscle cell-proliferation. Am. J. Physiol.-Lung Cell. Mol. Physiol. 13, L339-L343.
Nowak R., Dorn A., Bernstein H. G., Rinne A., Scholtz H. J. and Ziegler M. (1986) Immunocytochemical detection of peptides in the guinea pig cochlea. Arch. Otorhinolaryngol. 243, 36-38.
Oancea E. and Meyer T. (1998) Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals. Cell 95, 307-318.
Oancea E., Teruel M. N., Quest A. F. and Meyer T. (1998) Green fluorescent protein (GFP)-tagged cysteine-rich domains from protein kinase C as fluorescent indicators for diacylglycerol signaling in living cells. J. Cell Biol. 140, 485-498.
Okabe T., Hide M., Koro O. and Yamamoto S. (2000) Substance P induces tumor necrosis factor-alpha release from human skin via mitogen-activated protein kinase. Eur. J. Pharmacol. 398, 309-315.
Otsuka M. and Yoshioka K. (1993) Neurotransmitter functions of mammalian tachykinins. Physiol. Rev. 73, 229-308.
Owens D. F. and Kriegstein A. R. (1998) Patterns of intracellular calcium fluctuation in precursor cells of the neocortical ventricular zone. J. Neurosci. 18, 5374-5388.
Post C. and Paulsson I. (1985) Antinociceptive and neurotoxic actions of substance P analogues in the rat's spinal cord after intrathecal administration. Neurosci. Lett. 57, 159-164.
Qian J., Ramroop K., McLeod A., Bandari P., Livingston D. H., Harrison J. S. and Rameshwar P. (2001) Induction of hypoxia-inducible factor-1alpha and activation of caspase-3 in hypoxia-reoxygenated bone marrow stroma is negatively regulated by the delayed production of substance P. J. Immunol. 167, 4600-4608.
Reid M. S., Herrera-Marschitz M., Hokfelt T., Ohlin M., Valentino K. L. and Ungerstedt U. (1990) Effects of intranigral substance P and neurokinin A on striatal dopamine release - I. Interactions with substance P antagonists. Neuroscience 36, 643-658.
Ron D. and Kazanietz M. (1999) New insights into the regulation of protein kinase C and novel phorbol ester receptors. FASEB J. 13, 1658-1676.
Sanberg P. R., Emerich D. F., Aebischer P., Amisetti S. M., Ouellette W., Koutouzis T. K., Cahill D. W. and Norman A. B. (1993) Substance-P containing polymer implants protect against striatal excitotoxicity. Brain Res. 628, 327-329.
Santarelli L., Gobbi G., Debs P. C., Sibille E. L., Blier P., Hen R. and Heath M. J. S. (2001) Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function. Proc. Natl. Acad. Sci. USA 98, 1912-1917.
Saria A. (1999) The tachykinin NK1 receptor in the brain: pharmacology and putative functions. Eur. J. Pharmacol. 375, 51-60.
Schickinger B., Ehrenberger K., Felix D., Heiniger-Burki C., Imboden H., Davies W. E. and Felix H. (1996) Substance P in the auditory hair cells in the guinea pig. ORL J. Otorhinolaryngol. Relat. Spec. 58, 121-126.
Schwindinger W. F. and Robishaw J. D. (2001) Heterotrimeric G-protein beta gamma-dimers in growth and differentiation. Oncogene 20, 1653-1660.
Soltoff S. P. (1998) Related adhesion focal tyrosine kinase and the epidermal growth factor receptor mediate the stimulation of mitogen-activated protein kinase by the G-protein-coupled P2Y2 receptor. Phorbol ester or [Ca2+]i elevation can substitute for receptor activation. J. Biol. Chem. 273, 23110-23117.
Sozeri O., Vollmer K., Liyanage M., Frith D., Kour G., Mark G. E. and Stabel S. (1992) Activation of the C-Raf protein-kinase by protein-kinase-C phosphorylation. Oncogene 7, 2259-2262.
Spigelman I. and Puil E. (1991) Substance P actions on sensory neurons. Ann. NY Acad. Sci. 632, 220-228.
Spoendlin H. (1971) Degeneration behaviour of the cochlear nerve. Arch. Klin. Exp. Ohren Nasen Kehlkopfheilkd. 200, 275-291.
Spoendlin H. (1979) Sensory neural organization of the cochlea. J. Laryngol. Otol. 93, 853-877.
Stanfield P. R., Nakajima Y. and Yamaguchi K. (1985) Substance P raises neuronal membrane excitability by reducing inward rectification. Nature 315, 498-501.
Swanson K. D., Reigh C. and Landreth G. E. (1998) ATP-stimulated activation of the mitogen-activated protein kinases through ionotrophic P2X2 purinoreceptors in PC12 cells. Difference in purinoreceptor sensitivity in two PC12 cell lines. J. Biol. Chem. 273, 19965-19971.
Toullec D., Pianetti P., Coste H. et al. (1991) The bisindolylmaleimide Gf-109203X is a potent and selective inhibitor of protein-kinase-C. J. Biol. Chem. 266, 15771-15781.
Vanbiesen T., Hawes B. E., Luttrell D. K., Krueger K. M., Touhara K., Porfiri E., Sakaue M., Luttrell L. M. and Lefkowitz R. J. (1995) Receptor-tyrosine-kinase-mediated and G-beta-gamma-mediated map kinase activation by a common signaling pathway. Nature 376, 781-784.
Vaudry D., Pamantung T. F., Basille M., Rousselle C., Fournier A., Vaudry H., Beauvillain J. C. and Gonzalez B. J. (2002) PACAP protects cerebellar granule neurons against oxidative stress-induced apoptosis. Eur. J. Neurosci. 15, 1451-1460.
Venepalli B. R., Aimone L. D., Appell K. C. et al. (1992) Synthesis and substance P receptor binding activity of androstano[3,2-b]pyrimido[1,2-a]benzimidazoles. J. Med. Chem. 35, 374-378.
Villalba M., Bockaert J. and Journot L. (1997) Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway. J. Neurosci. 17, 83-90.
Way K. J., Chou E. and King G. L. (2000) Identification of PKC-isoform-specific biological actions using pharmacological approaches. Trends Pharmacol. Sci. 21, 181-187.
Webster M. and Wester D. B. (1981) Spiral ganglion neuron loss following organ of Corti loss: a quantitative study. Brain Res. 212, 17-30.
Whitty C. J., Kapatos G. and Bannon M. J. (1993) Neurotrophic effects of substance P on hippocampal neurons in vitro. Neurosci. Lett. 164, 141-144.
Wilkinson S. E., Parker P. J. and Nixon J. S. (1993) Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein-kinase-C. Biochem. J. 294, 335-337.
Xie P., Browning D. D., Hay N., Mackman N. and YeR. D. (2000) Activation of NF-kappa B by bradykinin through a G alpha(q)-and G beta gamma-dependent pathway that involves phosphoinositide 3-kinase and Akt. J. Biol. Chem. 275, 24907-24914.
Xu J., Weng Y. I., Simonyi A., Krugh B. W., Liaa Z., Weisman G. A. and Simoni A. (2002) Role of PKC and MAPK in cytosolic PLA2 phosphorylation and arachadonic acid release in primary murine astrocytes. J. Neurochem. 83, 259-270.
Yang C. M., Hsiao L. D., Chien C. S., Lin C. C., Luo S. F. and Wang C. C. (2002) Substance P-induced activation of p42/44 mitogen-activated protein kinase associated with cell proliferation in human tracheal smooth muscle cells. Cell Signal. 14, 913-923.
Yankner B. A., Duffy L. K. and Kirschner D. A. (1990) Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science 250, 279-282.
Yip J. and Chahl L. A. (1999) Distribution of Fos-like immunoreactivity in guinea-pig brain following administration of the neurokinin-1 receptor agonist, [Sar (9),Met (0-2) (11)] substance P. Neuroscience 94, 663-673.
Ylikoski J., Pirvola U., Happola O., Panula P. and Virtanen I. (1989) Immunohistochemical demonstration of neuroactive substances in the inner ear of rat and guinea pig. Acta Otolaryngol. 107, 417-423.
Yu Z. F., Cheng G. J., Huang X. F., Li K. Y. and Cao X. D. (1997) Neurokinin-I receptor antagonist SR140333: a novel type of drug to treat cerebral ischemia. Neuroreport 8, 2117-2119.
Zwick E., Daub H., Aoki N., Yamaguchi-Aoki Y., Tinhofer I., Maly K. and Ullrich A. (1997) Critical role of calcium-dependent epidermal growth factor receptor transactivation in PC12 cell membrane depolarization and bradykinin signaling. J. Biol. Chem. 272, 24767-24770.